Transcriptional and Cytokine Profiles Identify CXCL9 as a Biomarker of Disease Activity in Morphea

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dc.contributor.advisorJacobe, Heidien
dc.contributor.committeeMemberChong, Benjamin F.en
dc.contributor.committeeMemberSendelbach, Dorothyen
dc.creatorO'Brien, Jack Christopheren
dc.date.accessioned2019-08-02T19:23:52Z
dc.date.available2019-08-02T19:23:52Z
dc.date.created2017-06
dc.date.issued2017-03-31
dc.date.submittedJune 2017
dc.date.updated2019-08-02T19:23:52Z
dc.descriptionThe general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.en
dc.description.abstractInterferon-related pathways have not been studied in morphea and biomarkers are needed. We sought to characterize morphea serum cytokine imbalance and interferon-related gene expression in blood and skin to address this gap by performing a case-control study of 87 participants with morphea and 26 healthy controls. We used multiplexed immunoassays to determine serum cytokine concentrations, performed transcriptional profiling of whole blood and lesional morphea skin, and employed double-staining immunohistochemistry to determine the cutaneous cellular source of CXCL9. We found that CXCL9 was present at increased concentrations in morphea serum (p<0.0001) as were other T-helper 1 cytokines. CXCL9 serum concentration correlated with the modified localized scleroderma skin severity index (r=0.44, p=0.0001), a validated measure of disease activity. CXCL9 gene expression was also increased in inflammatory lesional morphea skin (Fold change 30.6, p=0.006), while preliminary transcriptional profiling showed little evidence for interferon signature in whole blood. Double-staining immunohistochemistry revealed CXCL9 co-localized with CD68+ dermal macrophages. In summary, inflammatory morphea is characterized by T-helper 1 cytokine imbalance in serum, particularly CXCL9, which is associated with disease activity. CXCL9 expression in lesional macrophages implicates the skin as the source of circulating cytokines. CXCL9 is a promising biomarker of disease activity in morphea.en
dc.format.mimetypeapplication/pdfen
dc.identifier.oclc1111292124
dc.identifier.urihttps://hdl.handle.net/2152.5/7088
dc.language.isoenen
dc.subjectChemokine CXCL9en
dc.subjectCytokinesen
dc.subjectGene Expression Regulationen
dc.subjectRNAen
dc.subjectScleroderma, Localizeden
dc.titleTranscriptional and Cytokine Profiles Identify CXCL9 as a Biomarker of Disease Activity in Morpheaen
dc.typeThesisen
dc.type.materialtexten
thesis.degree.departmentUT Southwestern Medical Schoolen
thesis.degree.disciplineResearchen
thesis.degree.grantorUT Southwestern Medical Centeren
thesis.degree.levelDoctoralen
thesis.degree.nameM.D. with Distinctionen

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